Effectiveness of lenvatinib versus sorafenib as first- or second-line therapy in hepatocellular carcinoma: insights from real-life data, systematic review, and meta-analysis
Rosanna Villani, Elisabetta Cornacchia, Nicolò Maria Sguera, Tommaso Colangelo, Tommaso Cassano, Danilo Di Bona, Gaetano ServiddioAbstract
Background
Clinical trials showed a non-inferior efficacy of lenvatinib versus sorafenib as first- or second-line treatment for advanced hepatocellular carcinoma (HCC). However, comparative effectiveness has not been definitively established. Our study aimed to compare the effectiveness of lenvatinib versus sorafenib as first-line therapy for advanced HCC in a real-world cohort and to integrate these findings with the available current evidence on the use of both drugs as first- or second-line therapy.
Methods
We conducted a propensity score-matched analysis including patients who were treated with lenvatinib or sorafenib as first-line therapy between January 2020 and December 2024. We also performed a systematic review and meta-analysis comparing the effectiveness of lenvatinib versus sorafenib as first-line therapy and a systematic review investigating the effectiveness of tyrosine-kinase inhibitor (TKI) as second-line therapy for advanced HCC.
Results
In our matched cohort (n = 84 patients), the patients treated with lenvatinib showed longer median overall survival than those treated with sorafenib (17.7 vs 11.2 months; P = 0.224). A meta-analysis of lenvatinib versus sorafenib as first-line therapy (n = 3,549 patients) demonstrated better outcomes for lenvatinib than for sorafenib in terms of overall survival, objective response rate, and disease control rate. In a proportional meta-analysis, lenvatinib showed a significantly higher objective response rate (38% vs 9%; P < 0.001) and a higher partial response rate (36% vs 9%; P < 0.001) than sorafenib. Results from the systematic review for TKI as second-line strategy (n = 1,011 patients) showed a trend toward better outcomes with lenvatinib, although limited data are available.
Conclusions
In the first-line setting, patients treated with lenvatinib had better clinical responses than did those treated with sorafenib. For second-line treatment, evidence is limited; however, available data show a trend toward better outcomes with lenvatinib and prospective studies are needed to confirm these findings.